U.S. Pat. No. 5,403,842, Leonardi et al., and its continuations in part (U.S. Pat. Nos. 5,474,994 and 5,605,896) claim heterobicyclic derivatives bearing substituted phenylpiperazines as basic moieties linked to the heterocyclic ring by a variety of spacer groups. Among said derivatives, compound A (Ex. 11) is of relevant interest due its very high uroselective activity. ##STR2##
Compound A is endowed with good affinity for the .alpha..sub.1A adrenoceptor and is able to selectively inhibit contractility of the prostatic urethra in a dog model without substantial effects on blood pressure (Leonardi et al., J. Pharmacol. Exp. Therap., 281:1272-1283, 1997.)
7-Oxo-7H-thieno[3,2-b]pyran-3-carboxylic acid and its N,.omega.-aminoalkylamides are compounds not yet reported in the literature. The present invention is directed to the new structural class of the N-(substituted phenyl)-N'-[.omega.-(5-substituted-7-oxo-7H-thieno[3,2-b]pyran-3-carbonyla mino)alkyl]piperazines.
Compounds of this class are endowed with enhanced selectivity toward the .alpha..sub.1 adrenergic receptor (with or without further selectivity for the .alpha..sub.1A receptor or for both .alpha..sub.1A and .alpha..sub.1D), in particular with respect to the 5-HT.sub.1A receptor, and improved in vivo uroselectivity even compared to compound A, with remarkable effects on relaxation of prostatic urethra and very low activity in lowering blood pressure. This activity profile suggests the safer use of the compounds of the invention in the therapy of obstructive syndromes of the lower urinary tract, including benign prostatic hyperplasia (BPH), and of lower urinary tract symptoms (LUTS) as well as of neurogenic lower urinary tract dysfunction (NLUTD), without side-effects associated with hypotensive activity.